Phase I Dose Escalation Study of VS-5584 in Subjects With Advanced Non-Hematologic Malignancies or Lymphoma

NCT01991938 | Terminated Phase 1

• 1 other identifier: VS-5584-101
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a Phase I, open-label, multicenter, dose-escalation trial of VS-5584, a PI3K/mTOR kinase inhibitor, in subjects with advanced non-hematologic malignancies or lymphoma. This clinical study is comprised of 2 sequential parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety (including the recommended Phase II dose), pharmacokinetics (the amount of VS-5584 in subject's blood) and the anti-cancer activity of VS-5584. Biomarkers (genes or proteins that may predict or show how subject's body may respond to VS-5584) will also be assessed in archival tumor tissue, tumor biopsies (in consenting subjects), and blood samples.

Conditions

Non Hematologic Cancers; Metastatic Cancer; Lymphoma

Keywords

PI3K Inhibitor; mTOR Inhibitor; Dual PI3K/mTOR Inhibitor; CSC; Cancer Stem Cells

Outcome Measures

Primary Outcomes (2)

• Assess the safety and tolerability of VS-5584 in subjects with advanced non-hematologic malignancies or lymphoma

  Serious Adverse events, Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECGs as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) V4.03. A Safety Monitoring Committee will review safety information.

  From start of treatment to end of treatment, an expected average of 6 weeks

• Determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) and schedule of VS-5584 administered to subjects with advanced non-hematologic malignancies or lymphoma

  The RP2D will be determined based on the MTD of VS-5584 as determined by number of participants with dose limiting toxicities related to VS-5584. Observations related to pharmacokinetics, pharmacodynamics, and any VS-5584 related toxicities may be included in the rationale supporting the RP2D and schedule and will not exceed the MTD.

  From start of treatment to end of Cycle 1 (21 day cycles)

Secondary Outcomes (1)

• Assess the pharmacokinetics of VS-5584

  Time points on Day 1, 2, 3, 17, 18

Other Outcomes (5)

• Evaluate the efficacy of VS-5584

  Every 6 weeks to end of treatment, expected average of 6 weeks

• Evaluate the time to new lesion

  Expected average of 6 weeks from start of treatment to end of treatment

• Evaluate duration of response to VS-5584 compared with duration of response to prior therapy

  Expected average of 6 weeks from start of treatment to end of treatment

Study Arms (1)

VS-5584

EXPERIMENTAL

Oral VS-5584 administered once daily on Day 1, 3, 5, 8, 10, 12, 15, 17 and 19 of each cycle

Drug: VS-5584

Interventions

VS-5584 DRUG

VS-5584

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide signed and dated informed consent prior to initiation of any study procedures.
• Age ≥ 18 years.
• Subjects must have a histopathologically confirmed diagnosis of an advanced non-hematologic malignancy or lymphoma or indolent NHL/CLL.
• Subjects must have no alternate therapy of proven benefit or have refused standard therapy.
• All clinically significant toxicities from prior chemotherapy must be ≤ Grade 1.
• ECOG performance status of 0 or 1, measured at screening and immediately before the start of treatment.
• Predicted life expectancy of ≥ 3 months.
• Fasting blood glucose of ≤ 140 mg/dL (7.8 mmol/L).
• Adequate renal function \[creatinine ≤ 1.5x ULN (upper limit of normal)\] or GFR of ≥ 60mL/min.
• Adequate hepatic function (total bilirubin ≤ 1.5x ULN for the institution; AST \[aspartate transaminase\] and ALT \[alanine transaminase\] ≤ 3x ULN).
• Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; platelets ≥ 75 x10\^9 cells/L; absolute neutrophil count ≥ 1.0x10\^9 cells/L).
• Corrected QT interval (QTc) \< 470 ms (as calculated by the Fridericia correction formula).
• Negative pregnancy test for women of child-bearing potential.
• Men and women of child bearing potential must agree to use adequate birth control throughout their participation in the study and for 60 days following the last study treatment.
• Willing and able to participate in the trial and comply with all trial requirements.

You may not qualify if:

• Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
• Uncontrolled or severe concurrent medical condition including cardiovascular disease (e.g., myocardial infarct, unstable angina, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, transient ischemic attacks, CVA, coronary artery or other vascular stents).
• A past history of, or current uncontrolled hypertension. Blood pressure must be adequately controlled prior to dosing with VS-5584.
• Prior history of a hypertensive reaction to a kinase inhibitor
• History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
• Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required).
• Subjects with known active Hepatitis A, B or C (testing not required).
• Subjects being actively treated for a secondary malignancy.
• Cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy with the exception of LHRH agonists for prostate cancer, biologic or immunotherapy, etc.) within 21 days of the first dose of study drug or 5 half-lives, whichever is shorter. Palliative radiotherapy is allowed prior to initiating treatment if associated toxicity resolved to ≤ Grade 1.
• Subjects currently taking medications known to be strong CYP3A4 inhibitors.
• Major surgery within 28 days prior to the first dose of study drug.
• Subjects with acute or chronic pancreatitis.
• Subjects with diabetes mellitus requiring insulin treatment or subjects with a HbA1C \> 7.
• Use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 14 days between termination of the investigational drug and administration of the study treatment is required. In addition, any drug-related toxicity except alopecia should have recovered to grade 1 or less.
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (5)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

The Royal Marsden

Sutton, London, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Lymphoma

Interventions

VS-5584

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: November 25, 2013
• Study Start: November 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 27, 2017

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); GB (1)